LY231514 is a novel multitargeted antifolate drug which has exhibited cytotoxic synergy, when combined sequentially with gemcitabine in cultured human carcinoma cell lines. Gemcitabine is a novel antimetabolite which inhibits DNA synthesis. It is our hypothesis that the combination of LY231514 and gemcitabine is a potent and effective antitumor treatment. We are undertaking a Phase I trial of LY231514 plus gemcitabine in patients with solid tumors refractory to standard therapy or for whom there is no standard treatment. The objectives of the trial are: 1) To determine the DLT of LY231514 and gemcitabine combination therapy, 2) to determine the recommended dose of LY231514 and gemcitabine combination therapy for subsequent clinical Phase II studies, 3) to collect information about the antitumor effects of LY231514 in combination with gemcitabine, 4) to determine if gemcitabine alters the disposition of LY231514. The eligibility criteria are metastatic or locally advanced cancer for which no therapy capable of cure or prolongation of survival; >18 years of age; performance status 0-2; life expectancy >12 weeks; adequate bone marrow, hepatic, and renal function; no prior LY231514 or gemcitabine; and no aspirin or other nonsteroidal anti-inflammatory agents administered <2 days before, during, and for 2 days after dosing with LY231514. Patients meeting the eligibility criteria will be gemcitabine administered intravenously over approximately 30 minutes on days 1 and 8 and LY231514 administered intravenously over 10 minutes on day 1 only. This cycle will be repeated every 21 days. The starting doses will be gemcitabine 1000 mg/m2 and LY231514 200 mg/m2. Doses of each drug will be escalated separately after three patients have been treated at each dose level without significant toxicity. Dose-limiting toxicity is defined as that dose in which >2/3 or >2/6 patients experienced >grade 3 nonhematologic or >grade 3 hematologic toxicities according to NCI CTC. The maximally tolerated dose is one dose level below that dose which causes dose-limiting toxicity. An exploratory analysis will be undertaken to related the pharmacokinetic parameters of this treatment and clinical or hematologic toxicity.